Haemodynamic Effects of Apelin Agonists and Antagonists in Man in COPD With Raised Pulmonary Artery Pressures

The purpose of this study:

To investigate the physiological role of apelin in the cardiovascular system in patients with COPD with raised pulmonary artery pressures.

Study Aim and hypotheses:

The primary objective is to test the above hypotheses using forearm blood flow and systemic infusions of apelin peptides.

Hypotheses:

• Apelin agonists are vasodilators in human resistance vessels and this effect will be altered in patients with pulmonary hypertension.
• Apelin peptides improve right ventricular and pulmonary haemodynamics in patients with elevated pulmonary artery pressures.

Study 1a - A validation dose study of 3 apelin agonists performed in healthy volunteers and COPD patients with elevated pulmonary artery pressures.

Study 1b- A validation dose study of apelin receptor antagonist, in healthy volunteers and COPD patients with elevated pulmonary artery pressures.

Study 2a - To define the haemodynamic response to apelin agonists in healthy volunteers and evaluate the response.

Study 2b - To investigate the haemodynamic response to 3 apelin agonists in COPD patients with elevated pulmonary artery pressures.

Inclusion criteria

• Healthy volunteers

• Aged 18 to 70 years
• Non-smoker (<1 cigarette per week)
• If female, postmenopausal or on days 2-9 of menstrual cycle and negative pregnancy test COPD patients with estimated Pulmonary Artery Pressure (PAP) on echo >25mmHg
• Clinical diagnosis of COPD as per standard criteria
• Between 18 and 70 years
• If female, postmenopausal or on days 2-9 of menstrual cycle and negative pregnancy test

Exclusion criteria

• pre-existing:

• Systemic Hypertension (sustained BP >160/100mmHg)
• Ischaemic Heart Disease
• Primary valvular heart disease
• Significant left ventricular failure
• Active malignancy
• Renal disease (Creatinine >180 µmol/L)
• Neurological disease
• Diabetes mellitus
• BMI >35, BMI <17
• Pregnancy
• Use of vasoactive medication or NSAIDS/aspirin within 48 hours of study.
• Current involvement in other research studies, other than observational/non-interventional
• Known HIV